Distress-mediated tissue oxidative stress was examined as a model of sub-healthy condition defined in traditional Chinese medicine theory. Mice were subjected to psychologically stressful conditions by whiskers removal. Under this condition, spontaneous locomotive activity was significantly enhanced in the dark (P < 0.05 versus the control mice in three different movements), and granulocytes/lymphocytes balance shifted to granulocytes. At the same time, peroxynitrite level in blood plasma increased to approximately 180% from that of the control mice at 6 h after removal of the whiskers (P < 0.01), and was maintained even after 12 h. Both protein carbonyl formation and lipid peroxidation were significantly increased under this condition in brain, heart, liver and spleen at 6 h after removal of whiskers (P < 0.05 or P < 0.01), and these levels were maximized after 12 h (increased to 120-160%, P < 0.05 or P < 0.01). The oxidative tissue injuries observed at 12 h after the removal of the whiskers were effectively prevented by two traditional Chinese medicine formula: Shengmai San (SMS) and Ling Gui Zhu Gan Tang (LGZGT), when administered for 5 days before the removal of the whiskers. Therefore, this stress model is considered useful in assessing the preventive potential of antioxidants and antioxidant-based herbal mixtures in treating the pathophysiology associated with psychological or emotional distress.